IMPORTANT SAFETY INFORMATION
SELARSDI™ (ustekinumab-aekn) Injection is contraindicated in patients with clinically significant hypersensitivity to ustekinumab products or to any of the excipients in SELARSDI.
Infections
Ustekinumab products may increase the risk of infections and reactivation of latent infections. Serious bacterial, mycobacterial, fungal, and viral infections were observed in patients receiving ustekinumab products. Serious infections requiring hospitalization or otherwise clinically significant infections were reported. In patients with plaque psoriasis, these included diverticulitis, cellulitis, pneumonia, appendicitis, cholecystitis, sepsis, osteomyelitis, viral infections, gastroenteritis, and urinary tract infections. In patients with psoriatic arthritis, this included cholecystitis. In patients with Crohn’s disease, these included anal abscess, gastroenteritis, ophthalmic herpes zoster, pneumonia, and Listeria meningitis. In patients with ulcerative colitis, these included gastroenteritis, ophthalmic herpes zoster, pneumonia, and listeriosis.
Treatment with SELARSDI should not be initiated in patients with a clinically important active infection until the infection resolves or is adequately treated. Consider the risks and benefits of treatment prior to initiating use of SELARSDI in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur while on treatment with SELARSDI and discontinue SELARSDI for serious or clinically significant infections until the infection resolves or is adequately treated.
Theoretical Risk for Vulnerability to Particular Infections
Individuals genetically deficient in IL-12/IL-23 are particularly vulnerable to disseminated infections from mycobacteria (including nontuberculous, environmental mycobacteria), Salmonella (including nontyphi strains), and Bacillus Calmette-Guerin (BCG) vaccinations. Serious infections and fatal outcomes have been reported in such patients. It is not known whether patients with pharmacologic blockade of IL-12/IL-23 from treatment with ustekinumab products may be susceptible to these types of infections. Consider diagnostic testing, eg, tissue culture, stool culture, as dictated by clinical circumstances.
Pre-Treatment Evaluation of Tuberculosis (TB)
Evaluate patients for TB prior to initiating treatment with SELARSDI. Do not administer SELARSDI to patients with active TB infection. Initiate treatment of latent TB before administering SELARSDI. Consider anti-tuberculosis therapy prior to initiation of SELARSDI in patients with a history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Closely monitor patients receiving SELARSDI for signs and symptoms of active TB during and after treatment.
Malignancies
Ustekinumab products are immunosuppressants and may increase the risk of malignancy. Malignancies were reported among patients who received ustekinumab in clinical trials. The safety of ustekinumab products has not been evaluated in patients who have a history of malignancy or who have a known malignancy. There have been post-marketing reports of the rapid appearance of multiple cutaneous squamous cell carcinomas in patients receiving ustekinumab products who had pre-existing risk factors for developing non-melanoma skin cancer (NMSC). All patients receiving SELARSDI, especially those greater than 60 years of age or those with a history of Psoralen plus ultraviolet A (PUVA) or prolonged immunosuppressant treatment, should be monitored for the appearance of NMSC.
Serious Hypersensitivity Reactions
Serious hypersensitivity reactions, including anaphylaxis and angioedema, have been reported with ustekinumab products in clinical trials and postmarketing. Some serious hypersensitivity reactions have occurred during the first intravenous dose of ustekinumab products. If severe or clinically significant hypersensitivity reaction occurs, discontinue SELARSDI immediately and initiate appropriate medical treatment.
Posterior Reversible Encephalopathy Syndrome (PRES)
Two cases of posterior reversible encephalopathy syndrome (PRES), also known as Reversible Posterior Leukoencephalopathy Syndrome (RPLS), were reported in clinical trials. Cases have also been reported in postmarketing experience in patients with psoriasis, psoriatic arthritis, and Crohn’s disease. Clinical presentation included headaches, seizures, confusion, visual disturbances, and imaging changes consistent with PRES a few days to several months after ustekinumab product initiation. A few cases reported latency of a year or longer. Patients recovered with supportive care following withdrawal of ustekinumab products.
Monitor all patients treated with SELARSDI for signs and symptoms of PRES. If PRES is suspected, promptly administer appropriate treatment and discontinue SELARSDI.
Immunizations
Prior to initiating therapy with SELARSDI, patients should receive all age-appropriate immunizations as recommended by current immunization guidelines. Patients being treated with SELARSDI should not receive live vaccines. Avoid administering BCG vaccines during treatment with SELARSDI or for one year prior to initiating treatment or one year following discontinuation of treatment. Caution is advised when administering live vaccines to household contacts of patients receiving SELARSDI because of the potential risk for shedding from the household contact and transmission to patient. Non-live vaccinations received during a course of SELARSDI may not elicit an immune response sufficient to prevent disease.
Concomitant Therapies
The safety of ustekinumab products, in combination with other biologic immunosuppressive agents or phototherapy, has not been evaluated in clinical trials of psoriasis. Ultraviolet-induced skin cancers developed earlier and more frequently in mice. In psoriasis studies, the relevance of findings in mouse models for malignancy risk in humans is unknown. In psoriatic arthritis studies, concomitant methotrexate use did not appear to influence the safety or efficacy of ustekinumab.
Noninfectious Pneumonia
Cases of interstitial pneumonia, eosinophilic pneumonia, and cryptogenic organizing pneumonia have been reported during post-approval use of ustekinumab products. Clinical presentations included cough, dyspnea, and interstitial infiltrates following one to three doses. Serious outcomes have included respiratory failure and prolonged hospitalization. Patients improved with discontinuation of therapy and, in certain cases, administration of corticosteroids. If diagnosis is confirmed, discontinue SELARSDI and institute appropriate treatment.
Allergen Immunotherapy
Ustekinumab products have not been evaluated in patients who have undergone allergy immunotherapy. Ustekinumab products may decrease the protective effect of allergen immunotherapy (decrease tolerance) which may increase the risk of an allergic reaction to a dose of allergen immunotherapy. Therefore, caution should be exercised in patients receiving or who have received allergen immunotherapy, particularly for anaphylaxis.
Most Common Adverse Reactions
The most common adverse reactions for plaque psoriasis and psoriatic arthritis (≥3%) were nasopharyngitis, upper respiratory tract infection, headache, and fatigue. The safety profile in pediatric patients with plaque psoriasis was similar to that of adults with plaque psoriasis. The most common adverse reaction for Crohn’s disease induction (≥3%) was vomiting. The most common adverse reactions for Crohn’s disease maintenance (≥3%) were nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, and sinusitis. The most common adverse reaction for ulcerative colitis induction (≥3%) was nasopharyngitis. The most common adverse reactions for ulcerative colitis maintenance (≥3%) were nasopharyngitis, headache, abdominal pain, influenza, fever, diarrhea, sinusitis, fatigue, and nausea.
